The role of NLRP3 inflammasome in the development of postoperative ileus and its molecular mechanism in male mice.

Abstract

This study investigated the roles of the NLRP3 inflammasome in postoperative ileus (POI) pathogenesis. Male BALB/c mice were randomly divided into sham, POI, and MCC950 (NLRP3 inhibitor) groups. Intestinal motility was assessed 24 h postoperatively. RNA-seq was performed. Histopathological changes were evaluated through H&E and immunofluorescence; CAT and POD activities in the intrinsic muscle layer were detected; Western blot was used to detect NLRP3, GSDMD-N, cleaved caspase-1, and p-NF-κB p65 expressions; ELISA was used to detect blood IL-1β, TNF-α, IL-6, and IL-10 levels. RNA-seq analysis showed 152 differential genes in the POI group, including NLRP3. In intestinal tissue of the POI mice, NLRP3 expression and expressions of GSDMD-N, cleaved caspase-1, and p-NF-κB p65 increased. IL-1β, TNF-α, IL-6, and IL-10 levels increased, while CAT, POD, and SOD activities decreased. The postoperative small intestine advancement rate of POI mice was reduced. After MCC950 intervention, the pathological damage to intestinal tissue and the intestinal function were restored, and the small intestine advancement rate was improved. Meanwhile, MCC950 effectively inhibited the activation of the NLRP3 inflammasome. NLRP3 inflammasome activation drives the pathogenesis of POI and MCC950 can effectively alleviate intestinal injury.